P361: HIGH REMISSION AND SURVIVAL RATE IN ADULTS WITH MINIMAL RESIDUAL DISEASE-POSITIVE OR RELAPSED/REFRACTORY B-CELL ACUTE LYMPHOBLASTIC LEUKAEMIA TREATED WITH BLINATUMOMAB IN ROUTINE CLINICAL PRACTICE
Authors: Sabina Chiaretti, Sabine Blum, Thibaut Leguay, Marie Balsat, Cyril Salek, Nicola Fracchiolla, Alexandros Spyridonidis, Anita Rijneveld, Cristina Papayannidis, Sofia Ganzha, Reetabrata Bhattacharyya, Gerhard Zugmaier, Isabella Pezzani Grueter, Andreas Ochs, Alessandro Rambaldi
Journal: HemaSphere (2023)

Background: This prospective observational study included adult patients (pts) who received blinatumomab for treatment of minimal residual disease-positive (MRD+) or relapsed/refractory (R/R) Philadelphia chromosome-negative (Ph-) B-cell ALL (including a subset of pts with late first relapse [LFR]) in routine clinical practice in 11 European countries. Aims: To describe 5-year interim analysis of effectiveness and safety data of blinatumomab in these pts. Methods: Adult pts who initiated blinatumomab between 28 December 2015 and 22 March 2022 were included. Treating clinicians categorised the disease state of pts at blinatumomab initiation as MRD+ or R/R (including LFR pts, defined as first remission duration of ≥12 months [mos]). Pts were followed-up until data cut-off (24 May 2022), death, loss-to-follow-up or withdrawal, whichever came first. Survival outcomes are estimated using Kaplan Meier (KM) methodology. Disease-free survival (DFS) in MRD+ pts is defined as time from blinatumomab initiation to relapse (>5% bone marrow blasts or blasts in peripheral blood) or death. Relapse-free survival (RFS) in R/R pts is defined as time from complete haematologic remission with full/partial/incomplete recovery (CR/CRh/CRi) to relapse or death. Overall survival (OS) is defined as time from blinatumomab initiation to death of any cause. Results: The analysis included 41 MRD+ and 158 R/R pts of whom 52 were LFR pts. Pts received a median of 2 cycles of blinatumomab. MRD+ pts’ median age was 41 years at blinatumomab initiation. At blinatumomab start, 70.7% (n=29) of patients were in first CR, 19.5% (n=8) and 4.9% (n=2) of pts received first or second salvage therapy, respectively. Three (7.3%) pts received prior haematopoietic stem-cell transplantation (HSCT). Within 2 blinatumomab cycles, among 31 pts evaluable for MRD, 67.7% (n=21) achieved a MRD response (MRD level <10-4). KM estimates for DFS and OS at 24 mos were 58.0% (95% confidence interval [CI]: 40-72) and 65.0% (95% CI: 44-80; Figure 1), respectively. Following blinatumomab treatment, 26 (63.4%) pts proceeded to allogeneic HSCT (alloHSCT). R/R pts’ median age at blinatumomab initiation was 48 years (41 for LFR pts). Before blinatumomab start, 60.1% (n=95) of pts had not received prior salvage, first and second salvage was received by 24.1% (n=38), and 8.2% (n=13), respectively. Prior HSCT was described for 19.6% (n=31) of pts (including 25.0% [n=13] LFR pts). Within 2 blinatumomab cycles, 75.3% (n=119) of pts achieved CR/CRh/CRi, including 82.7% (n=43) of LFR pts. Out of pts in CR/CRh/CRi evaluable for MRD response, 61.3% (n=73/119; 65.1% [n=28/43] of LFR) achieved a MRD response. RFS and OS at 24 mos were 48.0% (95% CI: 38-57; LFR: 65% [49-78]) and 51.0% (95% CI: 42-59; LFR: 74.0% [59-84]; Figure 1) respectively. Almost two-thirds (62.2%, n=74) of pts in CR/CRh/CRi, including 65.1% (n=28) of LFR pts, proceeded to alloHSCT. At data-cut-off, 61% (n=25) of MRD+ and 65.8% (n=104) of R/R pts including 71.2% (n=37) of LFR pts experienced treatment-related treatment-emergent adverse events (TEAEs). The most common (≥5%) serious TEAEs among the entire study population were cytokine release syndrome (8.4%) and neutropenia (5.4%).Summary/Conclusion: In real-world clinical practice, survival outcomes confirm blinatumomab as an effective therapy in pts with MRD+ and R/R Ph- B-cell ALL including those with LFR. Within 2 blinatumomab cycles, high MRD response rates were observed. Over two-thirds of pts with R/R Ph- ALL achieved CR/CRh/CRi and 62.2% of those R/R pts proceeded to alloHSCT. Overall, the benefit-risk profile of blinatumomab remains favourable. Keywords: Real world data, Relapsed acute lymphoblastic leukemia, MRD, Survival